Neutrophilic-chronic myeloid leukemia: low levels of p230 BCR/ABL mRNA and undetectable BCR/ABL protein may predict an indolent course.

Abstract

BACKGROUND:

Neutrophilic-chronic myeloid leukemia (CML-N) has been described as a CML variant associated both with a distinctive molecular defect of the Philadelphia chromosome and with a more benign clinical course than classic CML. The translocation (9;22) in CML-N results in the transcription of an e19/a2 type BCR/ABL mRNA that codes for a 230-kD BCR/ABL protein (p230). The indolence of the clinical course of patients with CML-N has been disputed.

METHODS:

The objectives of this study were to quantify and correlate with clinical outcome the p230 mRNA and protein in patients with CML-N, to describe six new patients and the follow-up (with molecular analysis) of five previously reported patients with CML-N, and to review characteristics of all patients with CML-N and p230 BCR/ABL reported to date in the literature.

RESULTS:

Quantitative polymerase chain reaction assays on specimens from the great majority of patients with CML-N revealed minimal numbers of molecules of p230 BCR/ABL transcripts per total RNA. This also was associated with a lack of detectable p230 BCR/ABL protein in patient specimens, even in one patient who was followed for 16 years after diagnosis. This may explain the milder leukemic phenotype in most patients with CML-N. A review of all 23 patients who had an e19/a2 type BCR/ABL translocation suggested that the low level of p230 BCR/ABL mRNA and the lack of detectable p230 BCR/ABL protein in patients with no additional cytogenetic abnormalities may predict their indolent clinical course.

CONCLUSIONS:

Patients with p230 positive CML-N have indolent course, probably as a result of low p230 mRNA and protein levels. This supports the need to conduct additional molecular studies, even if cytogenetic studies have revealed t(9;22), because of the prognostic importance of the molecular findings.

• Authors: Srdan Verstovsek, Hui Lin, Hagop Kantarjian, Giuseppe Saglio, Daniela De Micheli, Fabrizio Pane, Guillermo Garcia-Manero, Mariano Intrieri, Bruno Rotoli, Francesco Salvatore, Jie Q Guo, Moshe Talpaz, Giorgina Specchia, Gianni Pizzolo, Anna Marina Liberati, Jorge Cortes, Robert C Quackenbush, Ralph B Arlinghaus
• Journal: Cancer (Cancer) Vol. 94 Issue 9 Pg. 2416-25 (May 01 2002) ISSN: 0008-543X [Print] United States
• PMID: 12015767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10490

Chemical References

• Peptides
• RNA, Messenger
• p 230
• Fusion Proteins, bcr-abl

Topics

• Adult
• Aged
• Blotting, Western
• Cell Line
• Female
• Follow-Up Studies
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Leukemia, Neutrophilic, Chronic (genetics, physiopathology)
• Male
• Middle Aged
• Peptides (genetics)
• Philadelphia Chromosome
• Polymerase Chain Reaction
• RNA, Messenger (analysis)
• Translocation, Genetic